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WO2002088120A1 - Procede de production d'un antidiabetique - Google Patents

Procede de production d'un antidiabetique Download PDF

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Publication number
WO2002088120A1
WO2002088120A1 PCT/CZ2002/000024 CZ0200024W WO02088120A1 WO 2002088120 A1 WO2002088120 A1 WO 2002088120A1 CZ 0200024 W CZ0200024 W CZ 0200024W WO 02088120 A1 WO02088120 A1 WO 02088120A1
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WO
WIPO (PCT)
Prior art keywords
formula
group
compound
residue
ethyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CZ2002/000024
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English (en)
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WO2002088120B1 (fr
Inventor
Ales Halama
Ludmila Hejtmánková
Petr Lustig
Jindrich Richter
Lucie Srsnová
Josef Jirman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zentiva KS
Original Assignee
Leciva AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CZ20011502A external-priority patent/CZ20011502A3/cs
Priority claimed from CZ20011501A external-priority patent/CZ20011501A3/cs
Priority to HU0400091A priority Critical patent/HUP0400091A2/hu
Priority to EEP200300519A priority patent/EE200300519A/xx
Priority to PL02363738A priority patent/PL363738A1/xx
Priority to DE60218449T priority patent/DE60218449D1/de
Application filed by Leciva AS filed Critical Leciva AS
Priority to SK1445-2003A priority patent/SK14452003A3/sk
Priority to US10/475,099 priority patent/US7009057B2/en
Priority to EP02734989A priority patent/EP1387843B1/fr
Priority to AU2002311057A priority patent/AU2002311057A1/en
Publication of WO2002088120A1 publication Critical patent/WO2002088120A1/fr
Anticipated expiration legal-status Critical
Publication of WO2002088120B1 publication Critical patent/WO2002088120B1/fr
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • the present invention relates to a method of obtaining an intermediate, useful for the production of (+/-)-5-[[4-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl] methyl] -2, 4-thiazolidinedione (termed pioglitazone hereinafter) of formula I
  • Pioglitazone belongs to the thiazolidinedione group of antidiabetics. This compound and its antidiabetic properties were described in EP 193 256. Later it was found that its antidiabetic effect consists in reducing insulin resistance, thereby improving glucose availability without increasing insulin secretion, unlike most other antidiabetics. For these extraordinary characteristics this product is of great importance for the treatment of non- insulin dependent diabetes mellitus. Combining with insulin or other antidiabetics can further increase its effect.
  • the reactions are carried out in alkaline environment in organic solvents (e.g., dimethylformamide) .
  • organic solvents e.g., dimethylformamide
  • EP 193 256 discloses another reaction, which can be described by the following scheme
  • Z is a leaving group of general formula R 3 SO 3 wherein R 3 is an alkyl or aryl, with an alkali metal p-hydroxybenzaldehyde or p-formylphenolate, i.e. with a compound of general formula IX
  • a drawback of the above-described methods is necessity of pressure reduction of the double bond of compound XI, i.e. 5-(4-(2-(5-ethyl-2-pyridyl)ethoxy)benzylidene)-2,4- thiazolidinedione.
  • the following methods are known:
  • EP 257 781 reduction is carried out with hydrogen under catalysis with rather expensive palladium at the gauge pressure of 50 kg/cm 2 and the temperature of 50 °C with the yield of 64 %.
  • the solution in accordance with the present invention involves condensing 4- derivatized phenol or phenolate with a pyridine base of general formula III
  • R is an amino group-containing organic residue, selected from the group comprising a residue of general formula
  • R a is hydrogen or a protecting group, which is removed before further treatment, and a residue of general formula
  • R b represents a carboxy group either in the free acid form or in the form of a salt or ester or another functional derivative or the nitrile group CN
  • M represents a hydrogen atom or a an alkali metal, being subjected, before or after carrying out the condensation, to the following operations: a. diazotizing the amino group present in organic residue R b. converting the diazotised residue R into a derivative of 2-halopropionate or 2- halopropionitrile of formula
  • R b is as defined above and X is a halogen c. cyclizing the derivative of 2-halopropionate or 2-halopropionitrile with thiourea d. hydrolysing the resulting imine thus giving thiazolidinedione cycle Diazotizing
  • Diazotizing is preformed from the bromohydride of the respective aniline derivative or amino acid by drop-by-drop adding a solution of sodium nitrite in water at about 5 °C.
  • Cyclizing with thiourea is carried out in ethanol at its boiling point with subsequent separation of the product.
  • the condensation with 2-(5-ethyl-2-pyridyl)ethyl derivative itself is carried out in the presence of a base in the form of an alkali metal carbonate, hydroxide or hydride in an organic solvent or in a heterogeneous mixture of an organic solvent and water.
  • a base in the form of an alkali metal carbonate, hydroxide or hydride in an organic solvent or in a heterogeneous mixture of an organic solvent and water.
  • the temperature when performed in an organic solvent ranges between 50 and 130 °C.
  • the solvent can be evaporated, or, if it is a high-boiling solvent, water is added to the mixture.
  • the product is extracted with ethyl acetate.
  • R a is a leaving group
  • formula V represents a yet undisclosed compound.
  • the selection of the leaving group R a is not essential for further procedure. It can be selected among the groups such as acyl, n-alkyloxycarbonyl, tert-butyloxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, allyloxycarbonyl, 2- cyanoethoxycarbonyl, dimethylaminomethylenyl or hexa-2,4-dien-2,5-diyl.
  • R a can be an acyl group derived from lower aliphatic acids (Ci to C 4 ), such as acetyl, or from lower aromatic acids, such as benzoyl.
  • R° is a mineral or organic acid residue such as a halogen, HSO “ , NO 3 " , R ⁇ OO- or R ⁇ Os-, wherein R 1 represents hydrogen or a hydrocarbon residue, which can be advantageously used for the preparation of pioglitazone.
  • the hydrolysis itself is carried out with a mineral or organic acid of general formula HR° or with a base.
  • compound IV represents 4-(2-(5-ethyl-2- pyridyl)ethoxy) aniline, i.e. the free base (m is 0).
  • haloacids such as hydrochloric acid
  • hydrobromic acid is especially preferable for hydrolysis of compound of formula V, when R° represents Br and the product of formula IV, 4-(2-(5-ethyl-2-pyridyl)ethoxy)aniline hydrobromide, need not to be isolated.
  • Oxygen-containing mineral acids such as sulphuric acid can also be used in the hydrolysis.
  • Useful organic acids include alkyl- or arylsulfonic acids (such as methanesulfonic acid). Numerous carboxylic acids such as formic or acetic acids can be used for the hydrolysis.
  • the compound of formula IV is further treated in a known manner, i.e. by diazotizing, Meerwein reaction, cyclizing with thiourea and hydrolysing the imine. This method has been described in EP 193 256 and is here depicted in Scheme 1.
  • the starting compound can be the amino acid tyrosine, an inexpensive natural source of formula
  • Condensation of intermediate VI with base III can in this case be made in an organic polar solvent such as dimethylformamide or dimethylsulfoxide.
  • the reaction temperature is selected in dependence of the base employed in the range of from 70 to 130 °C.
  • the reaction time ranges, again in connection with the selected base, between 0.5 and 3 hours.
  • the reaction mixture is quenched with water and the product is extracted, usually with acetate.
  • R is a protected amine of formula -NHR a
  • the most preferable composition is the case when R a is acetyl, and the compound of formula II is widely used paracetamol.
  • the condensation in this case is preferably carried out in ethanol at 50 °C. After the reaction is complete, ethanol is evaporated and the product extracted with ethyl acetate.
  • 4-(2-(5-ethyl-2-pyridyl)ethoxy)acetaniline is obtained by hydrolysing 4-(2-(5-ethyl-2-pyridyl)-ethoxy)acetanilide as described in Example 1.
  • Tyrosine (20 g) is dissolved in HBr (100 ml, 48% diluted with 200 ml water). To the cooled solution NaNO 2 in 30 ml water is added drop wise. The product is extracted with ethyl acetate and after common treatment 2-bromo-3-(4-hydroxyphenyl)-propionic acid is obtained, which is used without purification for the next step.
  • the semi-solid residue is mixed in water and the solid portion of 5-[[4-[2-(5-ethyl-2-pyridyl) ethoxy]phenyl]methvl]-2.4-thiazolidinedione (0.18 g) is filtered off and recrystallized from the mixture DMF-water.
  • the mixture is mixed at 5 °C for another 20 mins, then acrylonitrile (16.8 ml) is added and the temperature is elevated to 38 °C. Cuprous oxide (0.5 g) is added in small portions.
  • the mixture is agitated until release of nitrogen stops, then concentrated under reduced pressure, the concentrate is alkalified by adding an aqueous ammonia solution and extracted with ethyl acetate. The ethylacetate layer is washed with water and dried over sodium sulfate.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Emergency Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Endocrinology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Saccharide Compounds (AREA)

Abstract

L'invention concerne un procédé de production d'un antidiabétique correspondant à la formule (I), consistant à faire condenser un phénol 4-dérivatisé ou un phénolate correspondant à la formule générale (II) où R représente un résidu organique contenant un groupe amino, choisi dans le groupe comprenant un résidu correspondant à la formule générale -NHRa, dans laquelle Ra représente hydrogène ou un groupe protecteur qui est enlevé avant le traitement ultérieur, ainsi qu'un résidu correspondant à la formule générale (i), dans laquelle Rb représente un groupe carboxy soit sous forme d'acide libre, soit sous forme d'un sel ou d'un ester, ou bien un autre dérivé fonctionnel ou le groupe nitrile CN, et M représente un atome d'hydrogène ou de métal alcalin, avec une base pyridique correspondant à la formule générale (III), dans laquelle Z représente un groupe partant autre qu'un halogène. Selon ledit procédé, avant ou après la condensation, on exécute les opérations suivantes : (a) diazotation du groupe amino présent dans le résidu organique R ; (b) conversion du résidu R diazoté en un dérivé de 2-halopropionate ou de 2-halopropionitrile correspondant à la formule (ii), dans laquelle Rb correspond à la définition donnée ci-dessus et X représente un halogène ; (c) cyclisation du dérivé de 2-halopropionate ou de 2-halopropionitrile avec de la thio-urée ; et (d) hydrolyse de l'imine obtenue, cette hydrolyse produisant la pioglitazone correspondant à la formule (I).
PCT/CZ2002/000024 2001-04-26 2002-04-25 Procede de production d'un antidiabetique Ceased WO2002088120A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
AU2002311057A AU2002311057A1 (en) 2001-04-26 2002-04-25 Method for obtaining pioglitazone as an antidiabetic agent
EP02734989A EP1387843B1 (fr) 2001-04-26 2002-04-25 Procede de production de pioglitazone comme antidiabetique
EEP200300519A EE200300519A (et) 2001-04-26 2002-04-25 Meetod pioglitasooni kui suhkurtõvevastase aine saamiseks
PL02363738A PL363738A1 (en) 2001-04-26 2002-04-25 Method for obtaining pioglitazone as an antidiabetic agent
DE60218449T DE60218449D1 (de) 2001-04-26 2002-04-25 Verfahren zur herstellung von pioglitazone als antidiabetisches mitttel
HU0400091A HUP0400091A2 (hu) 2001-04-26 2002-04-25 Eljárás antidiabetikus hatású pioglitazon előállítására
SK1445-2003A SK14452003A3 (sk) 2001-04-26 2002-04-25 Spôsob výroby pioglitazonu ako antidiabetika
US10/475,099 US7009057B2 (en) 2001-04-26 2002-04-25 Method for obtaining pioglitazone as an antidiabetic agent

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CZPV2001-1502 2001-04-26
CZ20011502A CZ20011502A3 (cs) 2001-04-26 2001-04-26 Způsob výroby antidiabetika
CZ20011501A CZ20011501A3 (cs) 2001-04-26 2001-04-26 Způsob výroby meziproduktu pro výrobu antidiabetika
CZPV2001-1501 2001-04-26

Publications (2)

Publication Number Publication Date
WO2002088120A1 true WO2002088120A1 (fr) 2002-11-07
WO2002088120B1 WO2002088120B1 (fr) 2004-02-26

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PCT/CZ2002/000024 Ceased WO2002088120A1 (fr) 2001-04-26 2002-04-25 Procede de production d'un antidiabetique

Country Status (11)

Country Link
US (1) US7009057B2 (fr)
EP (1) EP1387843B1 (fr)
AT (1) ATE355286T1 (fr)
AU (1) AU2002311057A1 (fr)
DE (1) DE60218449D1 (fr)
EE (1) EE200300519A (fr)
HU (1) HUP0400091A2 (fr)
PL (1) PL363738A1 (fr)
RU (1) RU2281285C2 (fr)
SK (1) SK14452003A3 (fr)
WO (1) WO2002088120A1 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004007490A3 (fr) * 2002-07-16 2004-03-25 Cadila Healthcare Ltd Procede de preparation de pioglitazone via plusieurs intermediaires.
ES2219180A1 (es) * 2003-05-09 2004-11-16 Medichem, S.A. Compuesto intermedio util para la preparacion de pioglitazona.
WO2004101560A1 (fr) * 2003-05-13 2004-11-25 Synthon B.V. Procedes de fabrication de derives de thiazolidinedione et composes associes
WO2004108721A1 (fr) * 2003-04-01 2004-12-16 Sun Pharmaceutical Industries Limited Procede servant a preparer 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione
WO2005021542A3 (fr) * 2003-08-28 2005-05-19 Ranbaxy Lab Ltd Procede pour la preparation de pioglitazone
WO2005080387A3 (fr) * 2004-02-20 2005-12-08 Synthon Bv Procedes pour produire de la pioglitazone et composes issus de ces procedes
CN1319956C (zh) * 2003-09-12 2007-06-06 深圳市海粤门生物科技开发有限公司 一种噻唑烷二酮的衍生物及其药用制剂的制备方法和应用
US7230016B2 (en) 2003-05-13 2007-06-12 Synthon Ip Inc. Pioglitazone salts, such as pioglitazone sulfate, and pharmaceutical compositions and processes using the same
KR100791400B1 (ko) 2006-09-06 2008-01-07 동우신테크 주식회사 티아졸리딘디온 유도체의 제조방법
US7402713B2 (en) * 2006-03-07 2008-07-22 E.I. Du Pont De Nemours And Company Processes for conversion of tyrosine to p-hydroxystyrene and p-acetoxystyrene
WO2009148195A1 (fr) * 2008-06-02 2009-12-10 Daebong Ls, Ltd. Composé de 5(4-hydroxybenzyl)thiazolidine-2,4-dione comme produit intermédiaire dans la synthèse de composés à base de thiazolidinedione et procédé de préparation de celui-ci
US8067450B2 (en) 2007-09-14 2011-11-29 Metabolic Solutions Development Company Thiazolidinedione analogues for the treatment of metabolic diseases
US8304441B2 (en) 2007-09-14 2012-11-06 Metabolic Solutions Development Company, Llc Thiazolidinedione analogues for the treatment of metabolic diseases
US8389556B2 (en) 2006-03-16 2013-03-05 Metabolic Soultions Development Company, LLC Thiazolidinedione analogues
US8629159B2 (en) 2006-03-16 2014-01-14 Metabolic Solutions Development Company, Llc Thiazolidinedione analogues
US8912335B2 (en) 2009-12-15 2014-12-16 Metabolic Solutions Development Company, Llc PPAR-sparing thiazolidinedione salts for the treatment of metabolic diseases
US8993773B2 (en) 2002-07-16 2015-03-31 Cadila Healthcare Limited Process to prepare pioglitazone via several novel intermediates
CN108003090A (zh) * 2018-01-05 2018-05-08 白银亿尔精细化工有限公司 一种制备4-[2-(5-乙基-2-吡啶基)乙氧基]硝基苯的方法

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0067718A1 (fr) * 1981-06-16 1982-12-22 Takeda Chemical Industries, Ltd. Dérivés de l'urée, leur préparation et application
EP0193256A1 (fr) * 1985-01-19 1986-09-03 Takeda Chemical Industries, Ltd. Dérivés de thiazolidinediones, leur préparation et utilisation
JPS62205054A (ja) * 1986-03-05 1987-09-09 Takeda Chem Ind Ltd 尿素誘導体
EP0816340A1 (fr) * 1996-06-27 1998-01-07 Takeda Chemical Industries, Ltd. Procédé pour la préparation de dérivés de 4-(2-(2-pyridyl)éthoxy)benzaldehyde
US20010008898A1 (en) * 2000-01-11 2001-07-19 Tsuyoshi Tomiyama Ether and amide compounds and preparation of thereof as antidiadetics.

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WO1986006069A1 (fr) * 1985-04-09 1986-10-23 Takeda Chemical Industries, Ltd. Derives de thiazolidinedione, leur procede de preparation et composition medicinale les contenant

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0067718A1 (fr) * 1981-06-16 1982-12-22 Takeda Chemical Industries, Ltd. Dérivés de l'urée, leur préparation et application
EP0193256A1 (fr) * 1985-01-19 1986-09-03 Takeda Chemical Industries, Ltd. Dérivés de thiazolidinediones, leur préparation et utilisation
JPS62205054A (ja) * 1986-03-05 1987-09-09 Takeda Chem Ind Ltd 尿素誘導体
EP0816340A1 (fr) * 1996-06-27 1998-01-07 Takeda Chemical Industries, Ltd. Procédé pour la préparation de dérivés de 4-(2-(2-pyridyl)éthoxy)benzaldehyde
US20010008898A1 (en) * 2000-01-11 2001-07-19 Tsuyoshi Tomiyama Ether and amide compounds and preparation of thereof as antidiadetics.

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DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; MASUMOTO, KEIICHI ET AL: "Preparation of phenylurea derivatives as herbicides", XP002211328, retrieved from STN Database accession no. 108:75006 *

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8445685B2 (en) 2002-07-16 2013-05-21 Cadila Healthcare Limited Process to prepare pioglitazone via several novel intermediates
US7863300B2 (en) 2002-07-16 2011-01-04 Cadila Healthcare Limited Process to prepare pioglitazone via several novel intermediates
WO2004007490A3 (fr) * 2002-07-16 2004-03-25 Cadila Healthcare Ltd Procede de preparation de pioglitazone via plusieurs intermediaires.
US7465801B2 (en) 2002-07-16 2008-12-16 Cadila Healthcare Limited Process to prepare pioglitazone via several novel intermediates
US7671207B2 (en) 2002-07-16 2010-03-02 Cadila Healthcare Limited Process to prepare pioglitazone via several novel intermediates
US8173816B2 (en) 2002-07-16 2012-05-08 Cadila Healthcare Limited Process to prepare pioglitazone via several novel intermediates
US8993773B2 (en) 2002-07-16 2015-03-31 Cadila Healthcare Limited Process to prepare pioglitazone via several novel intermediates
WO2004108721A1 (fr) * 2003-04-01 2004-12-16 Sun Pharmaceutical Industries Limited Procede servant a preparer 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione
ES2219180B1 (es) * 2003-05-09 2006-03-01 Medichem, S.A. Compuesto intermedio util para la preparacion de pioglitazona.
US7375231B2 (en) 2003-05-09 2008-05-20 Medichem S.A. Intermediate compound which is used for the preparation of pioglitazone
WO2004099147A1 (fr) * 2003-05-09 2004-11-18 Medichem, S.A. Compose intermediaire utilise pour la preparation de pioglitasone
ES2219180A1 (es) * 2003-05-09 2004-11-16 Medichem, S.A. Compuesto intermedio util para la preparacion de pioglitazona.
US7230016B2 (en) 2003-05-13 2007-06-12 Synthon Ip Inc. Pioglitazone salts, such as pioglitazone sulfate, and pharmaceutical compositions and processes using the same
WO2004101560A1 (fr) * 2003-05-13 2004-11-25 Synthon B.V. Procedes de fabrication de derives de thiazolidinedione et composes associes
WO2005021542A3 (fr) * 2003-08-28 2005-05-19 Ranbaxy Lab Ltd Procede pour la preparation de pioglitazone
CN1319956C (zh) * 2003-09-12 2007-06-06 深圳市海粤门生物科技开发有限公司 一种噻唑烷二酮的衍生物及其药用制剂的制备方法和应用
US7541470B2 (en) 2004-02-20 2009-06-02 Synthon Ip Inc. Processes for making pioglitazone and compounds of the processes
WO2005080387A3 (fr) * 2004-02-20 2005-12-08 Synthon Bv Procedes pour produire de la pioglitazone et composes issus de ces procedes
US7402713B2 (en) * 2006-03-07 2008-07-22 E.I. Du Pont De Nemours And Company Processes for conversion of tyrosine to p-hydroxystyrene and p-acetoxystyrene
US8389556B2 (en) 2006-03-16 2013-03-05 Metabolic Soultions Development Company, LLC Thiazolidinedione analogues
US8629159B2 (en) 2006-03-16 2014-01-14 Metabolic Solutions Development Company, Llc Thiazolidinedione analogues
KR100791400B1 (ko) 2006-09-06 2008-01-07 동우신테크 주식회사 티아졸리딘디온 유도체의 제조방법
US8067450B2 (en) 2007-09-14 2011-11-29 Metabolic Solutions Development Company Thiazolidinedione analogues for the treatment of metabolic diseases
US8304441B2 (en) 2007-09-14 2012-11-06 Metabolic Solutions Development Company, Llc Thiazolidinedione analogues for the treatment of metabolic diseases
WO2009148195A1 (fr) * 2008-06-02 2009-12-10 Daebong Ls, Ltd. Composé de 5(4-hydroxybenzyl)thiazolidine-2,4-dione comme produit intermédiaire dans la synthèse de composés à base de thiazolidinedione et procédé de préparation de celui-ci
US8912335B2 (en) 2009-12-15 2014-12-16 Metabolic Solutions Development Company, Llc PPAR-sparing thiazolidinedione salts for the treatment of metabolic diseases
US9126959B2 (en) 2009-12-15 2015-09-08 Metabolic Solutions Development Company, Llc PPAR-sparing thiazolidinedione salts for the treatment of metabolic diseases
CN108003090A (zh) * 2018-01-05 2018-05-08 白银亿尔精细化工有限公司 一种制备4-[2-(5-乙基-2-吡啶基)乙氧基]硝基苯的方法

Also Published As

Publication number Publication date
EP1387843B1 (fr) 2007-02-28
ATE355286T1 (de) 2006-03-15
RU2003134542A (ru) 2005-06-10
HUP0400091A2 (hu) 2004-06-28
US20050043360A1 (en) 2005-02-24
SK14452003A3 (sk) 2004-04-06
PL363738A1 (en) 2004-11-29
US7009057B2 (en) 2006-03-07
EP1387843A1 (fr) 2004-02-11
EE200300519A (et) 2004-02-16
RU2281285C2 (ru) 2006-08-10
WO2002088120B1 (fr) 2004-02-26
AU2002311057A1 (en) 2002-11-11
DE60218449D1 (de) 2007-04-12

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